CELL-ADHESION MOLECULES MEDIATE RADIATION-INDUCED LEUKOCYTE ADHESION TO THE VASCULAR ENDOTHELIUM

The predominant early histological changes in irradiated tissues are e dema and leukocyte infiltration. Cell adhesion molecules (CAMs) are re quired for the extravasation of leukocytes from the circulation, To st udy the role of CAMs in the pathogenesis of radiation-mediated inflamm ation, we quantified the expression of P-selectin, E-selectin, interce llular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecu le-1 glycoproteins on the surface of irradiated human endothelial cell s. We found that E-selectin and ICAM-1 expression increased after irra diation, whereas there was no increased expression of other cytokine-i nducible adhesion molecules (P-selectin or vascular cell adhesion mole cule-1). We found a dose- and time-dependent increase in radiation-ind uced expression of both E-selectin and ICAM-1. Furthermore, the thresh old dose for E-selectin expression was 1 Gy, whereas the threshold dos e for ICAM-1 synthesis was 5 Gy of X-rays. Northern blot analysis of R NA from irradiated endothelial cells demonstrated that ICAM-1 is expre ssed at 3-6 h following irradiation. No de novo protein synthesis was required for increased ICAM-1 mRKA expression. The 1.1-kb segment of t he 5' untranslated region of the ICAM-1 gene was sufficient for X-ray induction of chloramphenicol acetyltransferase reporter gene expressio n. We measured whether ICAM-1 mediates adhesion of leukocyte to the ir radiated endothelium and found that leukocyte adhesion occurred concur rently with ICAM-1 induction. Radiation-mediated leukocyte adhesion wa s prevented by anti-ICAM-1 blocking antibodies. These data indicate th at ICAM-1 participates in the inflammatory response to ionizing radiat ion. Moreover, radiation induction of these CAMs occurs in the absence of tumor necrosis factor and interleukin 1 production.